Campath-1H therapy: the impact of depletion resistent memory T cells on rejection and tolerance. (360G-Wellcome-080353_Z_06_A)

The future of transplantation lies in the development of strategies that result in donor-specific unresponsiveness or tolerance to the transplant whilst maintaining protection against foreign pathogens. Current drug therapy involves long-term treatment with globally immunosuppressive drugs that are associated with a spectrum of unwanted effects. Campath-1H, a powerful leucocyte depleting monoclonal antibody, has been shown to be able to reduce the dose of immunosuppressives used post-transplant, and in selective cases, cause donor-specific unresponsiveness. These findings, however, remain controversial, as long-term follow-up studies assessing the immune status of recipients have not been performed. The key goals of this study are to investigate the phenotype and function of leucocytes that repopulate the immune system after depletion, and to correlate the presence of certain lymphocyte subsets with rejection and donor-specific unresponsiveness. Preliminary data suggests that memory T cells (TM) are resistant to depletion and are uniquely present at the time of rejection. Therefore, the impact of these depletion resistant cells on rejection and established tolerance inducing protocols will be assessed in vivo in mice. This data will be used to design a strategy to control alloantigen-specific memory cells to allow for long-term graft survival.